HIV-Exposed Uninfected Infants Have Increased Regulatory T Cells That Correlate With Decreased T Cell Function
HIV-Exposed Uninfected Infants Have Increased Regulatory T Cells That Correlate With Decreased T Cell Function
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DOI：
10.3389/fimmu.2019.00595
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发表时间：
2019-03-26
影响因子：
7.3
通讯作者：
Weinberg, Adriana
中科院分区：
文献类型：
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作者：
Jalbert, Emilie;Williamson, Kayla M.;Weinberg, Adriana
背景资料：与未接触艾滋病毒的未感染婴儿（HUU）相比，接触艾滋病毒的未感染婴儿（HEU）发生严重感染、住院和死亡的风险更高，但其免疫缺陷的原因尚不清楚。为了解决这一差距，我们研究了T细胞的功能及其与T细胞和抗原呈递细胞（APC）在HEU和HUU.Methods表型配置文件的关系：从55 HEU和16 HUU的血液单核细胞刺激葡萄球菌肠毒素B（SE B）或模拟72小时，并通过流式细胞术检测增殖和表达的Th 1，Th 2和调节（Treg）标志物。结果：HEU对SEB/mock的CD 4+功能反应低于HUU，而CD 8+反应与HUU相似。在表型T细胞组中，与HUU相比，HEU显示更高比例的表达IL 10、F0 XP 3和CD 25的CD 4+和CD 8 + Treg;更高的效应Tconv和Treg;以及更低的初始和CD 4 + TGF β + Treg。在表型APC组中，与HUU相比，HEU显示出更高比例的CD 1c + cDC 2、CD 123 + pDC、CD 16+炎性单核细胞和cDC，以及更高的CD 103在CD 1c-CD 123-CD 16-cDC 1上的表达。针对HIV暴露调整的回归分析和多重比较显示，未刺激细胞中较高的CD 8 + IL 10+和CD 8 + FOXP 3 + Treg与对SEB/模拟的较低的CD 8 + T细胞功能应答相关。功能不受Tconv分化的影响，但更高的APC激活聚集与更高的CD 8 + IL 10 + Treg对SEB的反应相关。结论：与HUU相比，HEU中T细胞功能降低。高CD 8 + Treg比例是HEU和HUU中T细胞功能降低的最重要预测因素。
Background: HIV-exposed uninfected infants (HEU) are at higher risk of severe infections, hospitalizations and death compared with HIV-unexposed uninfected infants (HUU), but the immune deficit underlying it is not known. To address this gap, we investigated T cell functionality and its relationship to phenotypic profiles of T cells and antigen presenting cells (APC) in HEU and HUU.Methods: Blood mononuclear cells from 55 HEU and 16 HUU were stimulated with Staphylococcal Enterotoxin B (SEB) or mock for 72 h, and tested by flow cytometry for proliferation and expression of Th1, Th2, and regulatory (Treg) markers. In parallel, cells were phenotypically assessed for differentiation profiles of Treg, conventional T cell (Tconv) and APC in unstimulated cells.Results: HEU had lower CD4+ functional responses to SEB/mock and similar CD8+ responses compared with HUU. In the phenotypic T cell panel, HEU showed higher proportions of CD4+ and CD8+ Treg expressing IL10, FOXP3, and CD25; higher effector Tconv and Treg; and lower naive and CD4+ TGF beta+ Treg compared with HUU. In the phenotypic APC panel, HEU showed higher proportions of CD1c+ cDC2, CD123+ pDC, CD16+ inflammatory monocytes and cDC and higher expression of CD103 on CD1c-CD123-CD16-cDC1 compared with HUU. Regression analyses adjusted for HIV exposure and multiple comparisons showed that higher CD8+IL10+ and CD8+ FOXP3+ Treg in unstimulated cells were associated with lower CD8+ T cell functional responses to SEB/mock. Functionality was not affected by Tconv differentiation, but higher APC activation in aggregate was associated with higher CD8+ IL10+ Treg responses to SEB.Conclusions: T cell functionality was decreased in HEU compared with HUU. High CD8+ Treg proportions were the most important predictors of decreased T cell functionality in HEU and HUU.